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PMID: 16682495 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent.

The Journal of experimental medicine ·Vol. 203 ·No. 5 ·2006-05-15 ·Pages 1273-82

Galkina E, Kadl A, Sanders J, Varughese D, Sarembock IJ, Ley K

Abstract

Atherosclerosis is an inflammatory disease of large arteries. Flow cytometry of aortic cell suspensions showed that B and T lymphocytes and some macrophages and dendritic cells are already present in the adventitia of normal/noninflamed mouse aortas. Adoptively transferred lymphocytes constitutively homed to the aorta and resided within the adventitia up to 7 d after transfer. Lymphocyte trafficking into normal/noninflamed or atherosclerosis-prone aortas was partially L-selectin dependent. Antigen-activated dendritic cells induced increased T lymphocyte proliferation within the aorta 72 h after adoptive transfer. During progression of atherosclerosis in apolipoprotein-E-deficient mice, the total number of macrophages, T cells, and dendritic cells, but not B cells, increased significantly. This alteration in immune cell composition was accompanied by the formation of tertiary lymphoid tissue in the adventitia of atherosclerotic aortas. These results demonstrate that lymphocytes already reside within the normal/noninflamed aorta before the onset atherosclerosis as a consequence of constitutive trafficking. Atherosclerosis induces the recruitment of macrophages and dendritic cells that support antigen presentation.

MeSH Terms
Adoptive Transfer Animals Antigen Presentation/immunology Antigens/immunology Aorta/immunology,pathology Apolipoproteins E/deficiency,immunology Atherosclerosis/genetics,immunology,pathology Cell Movement/genetics,immunology Cell Proliferation Connective Tissue/immunology,pathology Dendritic Cells/immunology,pathology Inflammation/genetics,immunology,pathology L-Selectin/genetics,immunology Lymphocytes/immunology,pathology Lymphoid Tissue/immunology,pathology Macrophages/immunology,pathology Mice Mice, Knockout
Chemicals
Antigens Apolipoproteins E L-Selectin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Galkina Elena
Department of Biomedical Engineering, University of Virginia, Health Sciences Center, Charlottesville, VA 22908, USA.
Kadl Alexandra
Sanders John
Varughese Danielle
Sarembock Ian J
Ley Klaus
References (48)
48 references, click to expand
  1. Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways.
    Nat Med. 2004 Apr;10(4):416-21 PMID: 15034566
  2. Role of monocytes in atherogenesis.
    Physiol Rev. 2003 Oct;83(4):1069-112 PMID: 14506301
  3. Flow cytometry analysis of atherosclerotic plaque cells from human carotids: a validation study.
    Cytometry. 2000 Feb 1;39(2):158-65 PMID: 10679734
  4. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity.
    Cell. 1991 Dec 20;67(6):1033-6 PMID: 1760836
  5. Detection of vascular dendritic cells accumulating calcified deposits in their cytoplasm.
    Tissue Cell. 1998 Jun;30(3):383-8 PMID: 10091340
  6. Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice.
    Circulation. 2000 Dec 12;102(24):2919-22 PMID: 11113040
  7. Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes.
    J Cell Biol. 1988 Nov;107(5):1853-62 PMID: 2460470
  8. Ultrastructural identification of monocyte-derived foam cells in fatty streak lesions.
    Artery. 1980;8(3):208-14 PMID: 7213030
  9. Direct viewing of atherosclerosis in vivo: plaque invasion by leukocytes is initiated by the endothelial selectins.
    FASEB J. 2001 May;15(7):1149-57 PMID: 11344083
  10. Importance of primary capture and L-selectin-dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo.
    J Exp Med. 2001 Jul 16;194(2):205-18 PMID: 11457895
  11. Ultrastructural recognition of cells with dendritic cell morphology in human aortic intima. Contacting interactions of Vascular Dendritic Cells in athero-resistant and athero-prone areas of the normal aorta.
    Arch Histol Cytol. 1995 Aug;58(3):307-22 PMID: 8527238
  12. Monocytic origin of foam cells in human atherosclerotic plaques.
    Atherosclerosis. 1984 Dec;53(3):265-71 PMID: 6397199
  13. Innate and adaptive immunity in the pathogenesis of atherosclerosis.
    Circ Res. 2002 Aug 23;91(4):281-91 PMID: 12193460
  14. T lymphocytes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA-1.
    Arterioscler Thromb. 1992 Feb;12(2):206-11 PMID: 1531930
  15. Natural antibodies and the autoimmunity of atherosclerosis.
    Springer Semin Immunopathol. 2005 Mar;26(4):385-404 PMID: 15609021
  16. CD1d-dependent activation of NKT cells aggravates atherosclerosis.
    J Exp Med. 2004 Feb 2;199(3):417-22 PMID: 14744994
  17. Aorta-associated CD34+ hematopoietic cells in the early human embryo.
    Blood. 1996 Jan 1;87(1):67-72 PMID: 8547678
  18. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E.
    Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8264-8 PMID: 7667279
  19. Depletion of natural killer cell function decreases atherosclerosis in low-density lipoprotein receptor null mice.
    Arterioscler Thromb Vasc Biol. 2004 Jun;24(6):1049-54 PMID: 14988092
  20. T cell receptor antagonist peptides induce positive selection.
    Cell. 1994 Jan 14;76(1):17-27 PMID: 8287475
  21. B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice.
    Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1892-8 PMID: 12426221
  22. Innate and acquired humoral immunities to influenza virus are mediated by distinct arms of the immune system.
    Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2250-5 PMID: 10051627
  23. T lymphocytes in atherogenesis-functional aspects and antigenic repertoire.
    Cardiovasc Res. 2003 Oct 15;60(1):78-86 PMID: 14522409
  24. Atherosclerosis, autoimmunity, and vascular-associated lymphoid tissue.
    FASEB J. 1997 Nov;11(13):1199-207 PMID: 9367355
  25. Immune responses to the HLA-A*0201-restricted epitopes of tyrosinase and glycoprotein 100 enable control of melanoma outgrowth in HLA-A*0201-transgenic mice.
    J Immunol. 2001 Nov 1;167(9):4853-60 PMID: 11673489
  26. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque.
    Arteriosclerosis. 1986 Mar-Apr;6(2):131-8 PMID: 2937395
  27. Oligoclonal T cell expansions in atherosclerotic lesions of apolipoprotein E-deficient mice.
    Arterioscler Thromb Vasc Biol. 2000 Jan;20(1):10-7 PMID: 10634795
  28. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice.
    J Clin Invest. 2002 Mar;109(6):745-53 PMID: 11901183
  29. Identification and analysis of macrophage-derived foam cells from human atherosclerotic lesions by using a "mock" FL3 channel in flow cytometry.
    Cytometry. 1997 Oct 1;29(2):155-64 PMID: 9332822
  30. The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium.
    J Clin Invest. 2001 Nov;108(9):1307-14 PMID: 11696575
  31. Atherosclerosis--an inflammatory disease.
    N Engl J Med. 1999 Jan 14;340(2):115-26 PMID: 9887164
  32. Atherosclerosis. the road ahead.
    Cell. 2001 Feb 23;104(4):503-16 PMID: 11239408
  33. RAG-1-deficient mice have no mature B and T lymphocytes.
    Cell. 1992 Mar 6;68(5):869-77 PMID: 1547488
  34. Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins.
    J Clin Invest. 1999 Jan;103(1):117-28 PMID: 9884341
  35. IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis.
    J Clin Invest. 2004 Aug;114(3):427-37 PMID: 15286809
  36. Demonstration of immunoglobulin in the neighbourhood of advanced atherosclerotic plaques.
    Atherosclerosis. 1981 Jan-Feb;38(1-2):211-6 PMID: 7470201
  37. Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques.
    Atherosclerosis. 2004 Sep;176(1):101-10 PMID: 15306181
  38. The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice.
    Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2386-91 PMID: 16179593
  39. Inflammation in atherosclerosis.
    Nature. 2002 Dec 19-26;420(6917):868-74 PMID: 12490960
  40. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation.
    Arteriosclerosis. 1984 Jul-Aug;4(4):323-40 PMID: 6466191
  41. B7-1/B7-2 costimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low-density lipoprotein receptor-deficient mice.
    Circulation. 2004 Apr 27;109(16):2009-15 PMID: 15096453
  42. Detection of B cells and proinflammatory cytokines in atherosclerotic plaques of hypercholesterolaemic apolipoprotein E knockout mice.
    Scand J Immunol. 1999 Jul;50(1):25-30 PMID: 10404048
  43. Inflammation, atherosclerosis, and coronary artery disease.
    N Engl J Med. 2005 Apr 21;352(16):1685-95 PMID: 15843671
  44. Induction of secondary and tertiary lymphoid structures in the skin.
    Immunity. 2004 Nov;21(5):655-67 PMID: 15539152
  45. Emigration of monocyte-derived cells from atherosclerotic lesions characterizes regressive, but not progressive, plaques.
    Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11779-84 PMID: 15280540
  46. Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization.
    Immunity. 2004 Oct;21(4):561-74 PMID: 15485633
  47. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E.
    Science. 1992 Oct 16;258(5081):468-71 PMID: 1411543
  48. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice.
    Immunity. 1994 Jul;1(4):247-60 PMID: 7534203
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20052205
Published
2006-05-15
Epub
2006-00-08
Pages
1273-82
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2121208
Subset
IM
Grants
NHLBI NIH HHS · P01 HL055798 · United States
NHLBI NIH HHS · R01 HL058108 · United States
NHLBI NIH HHS · P01 HL55798 · United States
NHLBI NIH HHS · HL58108 · United States
External Links
PubMed source DOI: 10.1084/jem.20052205 PMC Full Text View journal details
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